interleukin-8 and Peripheral-Vascular-Diseases

Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation.. AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression.. Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive.. AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes.

Topics: Age Factors; Aged; Amputation, Surgical; Arthroplasty, Replacement, Knee; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Comorbidity; Cytokines; Diabetes Mellitus; Elective Surgical Procedures; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Leptin; Linear Models; Male; Middle Aged; Obesity; Peripheral Vascular Diseases; Phenotype; Plasminogen Activator Inhibitor 1; Polypharmacy; Prospective Studies; Resistin; Sex Factors; Subcutaneous Fat

The most commonly occurring atherosclerotic manifestations are peripheral artery diseases (PAD). Immune-mediated processes contribute to the development of atherosclerosis, and affect the diseases outcome. The aim of the present study was to assess various immune-competent cells, cytokines and chemokines in patients with PAD and to evaluate whether the base immunological values reflect the subsequent development of cardio/cerebrovascular symptoms. One hundred sixty patients with PAD were followed-up for 42 months. At the time of enrolment, we determined blood lymphocyte subpopulations, both T-helper (Th)1/Th2-type intracytoplasmic cytokines and soluble cytokines, chemokines. Intracellular cytokines were measured on phorbol-myristate-acetate- and ionomycine- stimulated cells. Lymphocyte subgroups were quantified by flow cytometry, soluble cytokines by ELISA and intracellular cytokine levels were measured by flow cytometry. The ankle-brachial index (ABI), indicator of atherosclerosis, was also evaluated. The clinical results were correlated with the immune-parameters to assess the input of immune-inflammatory events in the propagation of vascular manifestation. CD4(+) T-cell proportions in patients with PAD with cerebro- cardio-vascular manifestations were decreased, which further reduced in patients with fatal outcome. Of circulating chemokines, IL-8 (CXCL-8) was increased in patients with subsequent cerebro- cardio-vascular manifestations, compared to those without the symptoms, and further raised in patients with fatal outcome. The percentage of interferon (IFN)-gamma positive cells showed clear negative correlation with ABI. We conclude that altered peripheral lymphocyte subsets and cytokine/chemokine imbalance play important roles in the proinflammatory cascade and reflect disease severity in patients with PAD.

Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Cytokines; Female; Humans; Interleukin-8; Lymphocyte Activation; Male; Middle Aged; Peripheral Vascular Diseases; Risk Factors; T-Lymphocytes

We investigated angiotensin type 1 receptor (AT1R) expression and interleukin-8 (IL-8) productions in polymorphonuclear leukocytes obtained from patients with peripheral arterial disease (PAD) undergoing femoral endarterectomy. Subjects at high cardiovascular risk (high-risk subjects, HRS) and healthy controls (HC) were also enrolled. To this end, patients with PAD were studied 1 month before surgery, at the time of surgery, and 3 and 6 months after surgery. Polymorphonuclear leukocytes were obtained from venous blood and evaluated for AT1R expression at messenger RNA (mRNA) and protein level and IL-8 production (by means of enzyme-linked immunosorbent assay). At baseline, AT1R membrane expression was similar in cells from patients with PAD, HRS, and HC, whereas AT1R mRNA was similar in patients with PAD and HC and higher in HRS. During the follow-up period, AT1R expression progressively decreased both on the cell membrane and at the mRNA level. Both resting and stimulated production of IL-8 was lower in patients with PAD in comparison to HC and HRS and did not change during the follow up period. In PAD patients, femoral endarterectomy is associated with reduction of AT1R expression however with no apparent effect on IL-8 production. The relevance of such effects for cardiovascular protection deserves consideration.

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Apolipoproteins A; Apolipoproteins B; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Endarterectomy; Female; Femoral Artery; Gene Expression; Heptanoic Acids; Humans; Interleukin-8; Male; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Peripheral Vascular Diseases; Pyrroles; Receptor, Angiotensin, Type 1; Triglycerides

Monocytes and macrophages play a key role in the progression of atheromatous changes. The peroxisome proliferator-activated receptor gamma (PPAR gamma) can limit macroangiopathy through the control of cytokine transcription. The objectives of this study were to examine the influence of PPAR gamma and its agonist (rosiglitazone) on the TNFalpha, IL-6, IL-8 and IL-10 gene expression in monocytes of patients with diabetic macroangiopathy and to analyse obtained results in context of selected atherogenic factors ant direct indicators of endothelial lesion. TNFalpha, IL-6, IL-8, IL-10 and PPAR gamma gene expression was assessed in peripheral blood monocytes in 45 patients with type 2 diabetes before and following 22 weeks of rosiglitazone therapy (real-time PCR [Applied Biosystems]). As indicators of endothelial lesion, concentration of thrombomodulin (immunoassay [Diagnostica Stago]) and amount of circulating blood endothelial cells (immunofluorescence method with MoAb CLB-HEC19) were determined. Following rosiglitazone therapy, a statistically significant downward tendency of TNFalpha (p=0.026) and IL-8 (p=0.008) gene expression was noted. Before and following rosiglitazone treatment, PPAR gamma, IL-6 and IL-10 gene expression was undetectable in studied monocytes in vivo. In conclusion, TNFalpha and IL-8 play an important role in monocyte atherogenic activity. Rosiglitazone reduces monocyte proinflammatory readiness by influencing the expression of selected atherogenic cytokines (PPAR gamma-independent pathway).

Topics: Adult; Aged; Atherosclerosis; Cohort Studies; Diabetes Mellitus, Type 2; Down-Regulation; Endothelial Cells; Female; Gene Expression Regulation; Humans; Interleukin-8; Male; Middle Aged; Monocytes; Peripheral Vascular Diseases; PPAR gamma; Rosiglitazone; Thiazolidinediones; Tumor Necrosis Factor-alpha

to investigate the levels of interleukin-8 (IL-8) in patients with peripheral arterial occlusive disease (PAOD) and healthy control subjects both before and after an acute exercise test.. twenty-six patients with intermittent claudication and 22 matched healthy control subjects each had IL-8 levels measured before and after a standard acute treadmill-exercise test. Subjects walked for 10 min or until stopped by claudication pain. Serum IL-8 levels were measured before exercise was commenced and 1, 5 and 10 min after exercise was stopped.. patients with PAOD had statistically significantly higher levels of IL-8 than healthy control subjects, before and after an acute exercise test (p <0.00001, Mann-Whitney). Ratios of the change of IL-8 levels post-exercise showed a statistically significant difference at the post-5-min time point (p =0.005), showing a difference in the change of IL-8 levels at this time point between the patient group and control group.. The increased levels and the failure of the cytokine levels to fall by the same extent after exercise in the patient group may be due to a combination of increased neutrophil activation, reduced blood flow and increased cytokine production during ischaemia-reperfusion, which is not observed in the healthy controls.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Exercise Test; Female; Humans; Interleukin-8; Intermittent Claudication; Male; Middle Aged; Neutrophil Activation; Peripheral Vascular Diseases; Reference Values; Statistics, Nonparametric; Time Factors

We evaluated the plasma concentrations of platelet activation markers and platelet-derived microparticles (PMP) in patients with connective tissue diseases complaining of peripheral circulation disorders (n = 16) and studied the effect of ticlopidine hydrochloride (ticlopidine) on PMP generation. There were significant differences in the levels of PMP and a platelet activation marker between before and after treatment with ticlopidine (PMP: 695 +/- 393 vs. 354 +/- 206/10(4) platelets, p < 0. 01; platelet CD63: 9.13 +/- 5.64 vs. 5.22 +/- 2.74%, p < 0.05). On the other hand, markers of vascular endothelium, such as vascular endothelium-derived small vesicles and serum thrombomodulin levels, were not affected by the administration of ticlopidine. Levels of cytokines and soluble adhesion molecules remained unchanged by ticlopidine administration. These findings suggest that ticlopidine may be useful for the inhibition of PMP-dependent vascular damage in patients with connective tissue diseases complaining of peripheral circulation disorders.

Topics: Antigens, CD; Biomarkers; Blood Platelets; Connective Tissue Diseases; Endothelium, Vascular; Female; Fibrinolytic Agents; Humans; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-8; Male; Middle Aged; Peripheral Vascular Diseases; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Solubility; Subcellular Fractions; Tetraspanin 30; Ticlopidine; Vascular Cell Adhesion Molecule-1

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aortic Diseases; Capillary Permeability; Citrates; Citric Acid; Erythrocytes; Female; Gallium Radioisotopes; Humans; Inflammation Mediators; Interleukin-8; Lung; Male; Middle Aged; Neutrophil Activation; Peptidyl-Dipeptidase A; Peripheral Vascular Diseases; Postoperative Complications; Radionuclide Imaging; Reperfusion Injury; Respiratory Distress Syndrome; Sodium Pertechnetate Tc 99m